Apigenin is one of the flavonoids - more precisely one of the citrus bioflavonoids. Just like most flavonoids, it has antioxidant, anti-inflammatory, and anti-tumor properties. Perhaps apigenin can even block the formation of uric acid leading to beneficial effects in gout.
Apigenin is found in high amounts in several herbs including parsley, thyme, and peppermint. It is is also found in a number of other herbs, including chamomile herb, Horsetail herb, lemon balm herb, perilla herb, vervain herb, and yarrow. Red wine and tomato sauce contain this flavonoid, also.
You can purchase chamomile extract herbal supplement online.
Which supplement would you recommend to get the highest
concentration of apigenin and/or hesperetin?
Chamomile and thyme appear to be good sources.
Benefits of apigenin
As with many flavonoids, it has potential to reduce the risk of cancer since it has anti-tumor activity. Apigenin also could potentially be useful in allergy conditions since it can have anti-inflammatory properties.
Antidepressant-like effects of apigenin and 2,4,5-trimethoxycinnamic acid from Perilla frutescens plant in the forced swimming test.
Biol Pharm Bull. 2003.
We studied the effects of apigenin and 2,4,5-trimethoxycinnamic acid on the behavioral despair test (forced swimming test), and the central noradrenergic, dopaminergic and serotonergic activities in mice. Behavioral and biochemical results indicate its antidepressant properties which may be mediated by the dopamine effects in the mouse brain.
Apigenin and its impact on gastrointestinal cancers.
Mol Nutr Food Res. 2013. Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada.
Apigenin is a flavonoid found in many fruits, vegetables, and herbs, the most abundant sources being the leafy herb parsley and dried flowers of chamomile. Present in dietary sources as a glycoside, it is cleaved in the gastrointestinal lumen to be absorbed and distributed as apigenin itself. For this reason, the epithelium of the gastrointestinal tract is exposed to higher concentrations of apigenin than tissues at other locations. This would also be true for epithelial cancers of the gastrointestinal tract. We consider the evidence for actions of apigenin that might hinder the ability of gastrointestinal cancers to progress and spread. It has been shown to inhibit cell growth, sensitize cancer cells to elimination by apoptosis, and hinder the development of blood vessels to serve the growing tumor. It also has actions that alter the relationship of the cancer cells with their microenvironment. Apigenin is able to reduce cancer cell glucose uptake, inhibit remodeling of the extracellular matrix, inhibit cell adhesion molecules that participate in cancer progression, and oppose chemokine signaling pathways that direct the course of metastasis into other locations.
Dr. Margaret A. Gates, of Brigham and Women's Hospital and Harvard Medical School, in Boston, Massachusetts, reviewed the foods commonly eaten over a one-week period by 1,140 women with ovarian cancer and 1,180 women without. From this information Dr. Margaret A. Gates and her team calculated the women's intake of 5 common flavonoids -- myricetin, kaempferol, quercetin, luteolin, and apigenin -- frequently obtained by drinking tea or red wine, or eating apples, romaine or leaf lettuce, kale, blueberries, oranges, celery, or tomato sauce. There was no connection between total flavonoid intake and ovarian cancer risk. Only apigenin intake was associated with a suggestive decrease in ovarian cancer risk. International Journal of Cancer, 2009.
Consuming foods like celery and parsley which contain the naturally occurring flavonoid apigenin may reduce the risk for leukemia. Maikel Peppelenbosch of the University of Groningen in the Netherlands said in January 2010 that apigenin was able to slow the development of two kinds of cells in leukemia and cut their survival chances. The findings suggest apigenin could hold promise for preventing leukamia. Maikel Peppelenbosch cautioned that his study had also found the compound has chemotherapy resistance properties, suggesting it might interfere with standard treatments for people already diagnosed with leukemia so it should not be taken at the same time as chemotherapy for established disease as it could interfere with the positive effects of treatment.
Synergistic interaction between hesperidin, a natural flavonoid, and diazepam.
Eur J Pharmacol. 2005.
It has been recently reported the presence in Valeriana of the flavone 6-methylapigenin and the flavanone glycoside hesperidin. The apigenin derivative is a ligand for the benzodiazepine binding site in the gamma-aminobutyric acid receptor type A (GABA(A)) and has anxiolytic properties. Hesperidin has sedative and sleep-enhancing properties but is not a ligand for the benzodiazepine binding site. 6-Methylapigenin is able to potentiate the sleep-enhancing effect of hesperidin. In this work we demonstrate that this property is shared with various GABA(A) receptor ligands, among them the agonist diazepam, which was used to study the potentiation as measured in the hole board test. Isobolar analysis of the results showed the interaction being synergistic. We discarded pharmacokinetic effects or a direct action of hesperidin on the benzodiazepine binding site. A possible use of hesperidin properties to decrease the effective therapeutic doses of benzodiazepines is suggested.
Dietary flavonoids as proteasome inhibitors and apoptosis
inducers in human leukemia cells.
Biochem Pharmacol. 2005 . Barbara Ann Karmanos Cancer Institute, and Department of Pathology, School of Medicine, Wayne State University, Detroit, MI
It has been shown that proteasome activity is required for cancer cell survival and consumption of fruits and vegetables is associated with decreased cancer risk. Previously, we reported that grape extract could inhibit proteasome activity and induce apoptosis in tumor cells. In this study, we examined the flavonoids apigenin, quercetin, kaempferol and myricetin for their proteasome-inhibitory and apoptosis-inducing abilities in human tumor cells. Our results suggested that the proteasome may be a target of these dietary flavonoids in human tumor cells and that inhibition of the proteasome by flavonoids may be one of the mechanisms responsible for their cancer-preventive effects.
Apigenin inhibits VEGF and HIF-1 expression via PI3K/AKT/p70S6K1
and HDM2/p53 pathways.
FASEB J. 2005. The Mary Babb Randolph Cancer Center, Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, West Virginia
Apigenin is a nontoxic dietary flavonoid that has been shown to possess anti-tumor properties and therefore poses special interest for the development of a novel chemopreventive and/or chemotherapeutic agent for cancer. Our findings reveal a novel role of apigenin in inhibiting HIF-1 and VEGF expression that is important for tumor angiogenesis and growth, identifying new signaling molecules that mediate this regulation.
Ibuprofen and apigenin induce apoptosis and cell cycle
arrest in activated microglia.
Neurosci Lett. 2005.
In case of injury or disease, microglia are recruited to the site of the pathology and become activated as evidenced by morphological changes and expression of pro-inflammatory cytokines. Evidence suggests that microglia proliferate by cell division to create gliosis at the site of pathological conditions such as the amyloid plaques in Alzheimer's disease and the substantia nigra of Parkinson's disease patients. The hyperactivation of microglia contributes to neurotoxicity. In the present study we tested the hypothesis that anti-inflammatory compounds modulate the progression of cell cycle and induce apoptosis of the activated cells. We investigated the effects of ibuprofen (non-steroidal anti-inflammatory drug) and apigenin (a flavonoid with anti-inflammatory and anti-proliferative properties) on the cell cycle of the murine microglial cell line BV-2. The findings indicate that apigenin-induced cell cycle arrest preferentially in the G2/M phase and ibuprofen caused S phase arrest. The binding of annexin V-FITC to the membranes of cells which indicates the apoptotic process were examined, whereas the DNA was stained with propidium iodide. Both apigenin and ibuprofen induced apoptosis significantly in early and late stages. The induction of apoptosis by ibuprofen and apigenin was confirmed using TUNEL assay, revealing that 25 microM apigenin and 250 microM ibuprofen significantly increased apoptosis in BV-2 cells. The results from the present study suggest that anti-inflammatory compounds might inhibit microglial proliferation by modulating the cell cycle progression and apoptosis.
Flavonoid apigenin inhibits motility and invasiveness of
carcinoma cells in vitro.
Int J Cancer. 2005.
Investigations of the mechanisms of the cancer-preventive activity of apigenin (4',5,7,-trihydroxyflavone), a plant-derived, anti-carcinogenic flavonoid, showed its interference with cell proliferation, survival, and gap junctional coupling. We used a model based on non-invasive HeLa wild-type cells and their connexin43 (Cx43) transfected counterparts to correlate the effect of apigenin on tumour cell invasiveness with its influence on cell motility. Both cell lines displayed similar motile properties in control conditions. Apigenin treatment resulted in a significant and reversible inhibition of translocation of both HeLa wild-type cells and HeLa Cx43 transfectants. The effect of apigenin on cell proliferation was less pronounced especially at low apigenin concentration, whereas its influence on cell motility correlated with the reduction of the invasive potential of HeLa Cx43 cells as shown by an invasion assay based on the confrontation of tumour cell spheroids with chick embryo heart fragments. HeLa Cx43 cells were highly invasive in controls, but did not invade the heart tissue at tumour cell aggregate-fibroblast capsule interfaces in the presence of apigenin and failed to fully engulf these heart fragments. Because the motility of chick heart fibroblasts was only slightly affected by apigenin, these observations indicate that apigenin exerts its anti-invasive effect on HeLa cells predominantly via a specific inhibition of tumour cell motility. This inhibitory effect of apigenin on tumour cell invasiveness in vitro demonstrates that apigenin may exert its anti-tumorigenic effect in vivo via inhibition of tumour cell penetration of the healthy tissue.
Apigenin induced apoptosis through p53-dependent pathway in human cervical cancer cells.
Life Sci. 2005.
Apigenin is a widely distributed plant flavonoid and was proposed as an antitumor agent. In this study, we reported for the first time that apigenin inhibited the growth of human cervical carcinoma cells (HeLa) and through apoptotic pathway. The results showed that apigenin significantly decreased the viability of HeLa cells at 37-74 microM and the IC50 value was 35.89 microM. Apigenin-induced apoptosis in HeLa cells was confirmed by DNA fragmentation assay and induction of sub-G1 phase by flow cytometry. Apigenin-treated HeLa cells were arrested at G1 phase, which was associated with a marked increment of the expression of p21/WAF1 protein. The induction of p21/WAF1 appeared to be transcriptionally upregulated and was p53-dependent. In addition, apigenin induced Fas/APO-1 and caspase-3 expression which were also correlated with apoptosis. Apigenin decreased in the protein expression of Bcl-2 protein, which is an anti-apoptotic factor. The conclusion of this study is the apigenin induced p53 expression which caused cell cycle arrest and apoptosis. These findings suggest that apigenin has strong potential for development as an agent for preventing cervical cancer.
Decreased pro-inflammatory cytokine production by
LPS-stimulated PBMC upon in vitro incubation with the flavonoids apigenin,
luteolin or chrysin, due to selective elimination of monocytes / macrophages.
Biochem Pharmacol. 2005.
Apigenin and its structural analogues chrysin and luteolin were used to evaluate their capacity to inhibit the production of pro-inflammatory cytokines by lipopolysaccharide (LPS)-stimulated human peripheral blood mononuclear cells (PBMC). Furthermore, flowcytometric analysis was performed to compare the effects of apigenin, chrysin, luteolin, quercetin and naringenin on the different cell types present in PBMC. LPS-stimulated PBMC were cultured in the presence of the flavonoids and TNFalpha, IL-1beta and IL-6 were measured in the supernatants. In parallel, metabolic activity of the PBMC was determined by measuring succinate dehydrogenase activity. Apigenin, chrysin and luteolin dose-dependently inhibited both pro-inflammatory cytokine production and metabolic activity of LPS-stimulated PBMC. With increasing concentration of apigenin, chrysin or luteolin the monocytes/macrophages disappeared as measured by flowcytometry. This also appeared to occur in the non-LPS-stimulated PBMC. At the same time there was an increase in dead cells. T- and B-lymphocytes were not affected. Quercetin and naringenin had virtually no effects on cytokines, metabolic activity or on the number of cells in the studied cell populations. In conclusion, monocytes were specifically eliminated in PBMC by apigenin, chrysin or luteolin treatment in vitro at low concentrations (around 8 microM), in which apigenin appeared to be the most potent.
luteolin and apigenin inhibit in vitro antigen-specific
proliferation and interferon-gamma production by murine and human autoimmune T
Biochem Pharmacol. 2004.
Flavonoids such as luteolin, fisetin and apigenin are inhibitors of
interleukin-4 and interleukin-13 production by activated human basophils.
Int Arch Allergy Immunol. 2004.
Molecular modeling of flavonoids that inhibits xanthine oxidase.
Biochem Biophys Res Commun. 2002.
The inhibition of xanthine oxidase activity by various flavonoids was assessed. All of the tested flavonoids were competitive inhibitors, and from the kinetic analysis suggested that flavonoids bind to the reactive site. To further understand the stereochemistry between these flavonoids and xanthine oxidase, structure-based molecular modeling was performed. Apigenin was the most potent inhibitor.
Q. Can a flavonoid supplement such as apigenin be used with tongkat ali LJ100?
A. Probably, but keep dosages low.
Q. Excellent review of the pathways associated with
apigenin, Luteolin- flavones etc. Briefly, I find apigenin in combination with the other flavonoids to be an exciting
treatment for prostate cancer patients, specific to inhibiton of fatty acids
synthase activity /angiogenesis. However, can we get
enough of the flavonoids in the olive leaf product to mount a successful
campaign? I believe, with synergy, we will need at least 1gram of apigenin
A. It is difficult to know at this time with hardly any research done with apigenin and prostate cancer. Perhaps many types of flavonoids would help beside apigenin. Please see the prostate cancer page for updates.
Q. There is a great deal of very promising information
about the potential value of apigenin at doses of about 150 mg/day in animal
models of prostate cancer, and there are no apparent toxicities. However, I
cannot find a source for apigenin in anything but trivial quantities. Do you
know of such a source?
A. I am not aware of any particular supplement companies that make an apigenin supplement product by itself.
Q. The U.S.D.A says that apigenin is an
Inhibitor. Do you have any info on that.
A. I have not come across human studies regarding the in vivo effect of apigenin supplements in terms of aromatase inhibition. There have been some in vitro and animal studies that indicate apigenin and other flavonoids to have aromatase inhibiting activity, but whether these flavonoids, when ingested as supplements, have a significant effect in humans has yet to be fully elucidated.
On your apigenin page, a reader asked where to find this
supplement in non-trivial quantities. I have had this same problem, since the
most common formulation is chamomile extract standardized to 1.5% Apigenin.
That's better than nothing but probably not much more than can be obtained
dietarily through chamomile tea or broccoli. I, and probably others, would like
to find a more potent form in case it would work therapeutically in ways similar
to lab and animal studies reported recently. (Of course I realize that there are
many questions of bioavailability and delivery that have not been addressed
yet.) Recently I have seen advertising for 50-mg Apigenin capsules from Swanson.
Their standard supplement label lists Apigenin 50 mg and no other measureable
ingredients so I assume it is fairly pure. However theirs is extracted from
grapefruit. Does it make any difference what food product Apigenin comes from?
Probably not, as long as the quality of the product is good and the capsules do contain the actual ingredient, it should not matter where it is derived from.
Is there any research you know of that would suggest the
minimum oral intake of apigenin to have an appreciable effect on, for example,
residual OvCa cells present during post-chemotherapy remission? I have found
several interesting mouse studies but I have no idea whether a daily dose of 50
or 100 mg would be likely to produce any effect in a human subject. Please
understand I am not asking for medical advice, just looking for existing
information that might be useful for reaching our own conclusions.
I am not aware of such research as of December 2009.